For the treatment of a wide variety of different nervous and mental diseases, and drug addictions, it is desirable to be able to effectively (both from the technological and cost standpoints) monitor the effectiveness of drugs and substances that affect brain chemistry. For instance in the treatment of schizophrenia, it is highly desirable to be able to gauge the brain biochemical effects of a dose of a neuroleptic drug (such Haloperidol) administered for blocking the patient's dopamine receptors, since if too little of the drug is administered the desired blockade does not occur, and if too much of the drug is administered there are severe side effects. Since less than one percent of the administered drug is bound by the neuroreceptors, it is difficult to determine by analysis of bodily fluids and discharges, and the like, how effective the treatment is for a particular patient. Similarly, in the treatment of drug addicts as, for example, in a methadone treatment program, it is desirable to obtain the optimum dosage for a given patient as quickly as possible, and if withdrawal symptoms occur, to change dosage as necessary.
According to the present invention, a method and apparatus are provided which provide for technological and cost-effective monitoring of the effectiveness of drugs and substances that affect brain chemistry so that the dosage of drugs affecting brain chemistry (such as in the treatment of nervous and mental disorders, and drug addiction) can be optimized. The invention has wide applicability, being applicable to dopamine, serotonin, opiate, and other neuroreceptors, can utilize a wide variety of radioactive tracer substances, such as carbon 11, fluorine 18, nitrogen 13, and oxygen 15, and can utilize a wide variety of apparatus.
According to the present invention, the most inexpensive, yet effective, apparatus is only a fraction of the cost of a positron-emission tomography (PET) scanner, and can detect microcurie doses of radiation, as opposed to millicurie doses that are needed for PET scanners. The preferred apparatus comprises a support structure for supporting a patient in a supine position, including a head support. First and second gamma ray directional detectors, such as NaI or BiGe detectors, are provided and are mounted so that one is operatively positioned on either side of the patient's head when supported by the head support. Lead collinators, or the like, may be provided to limit the field of view of the detectors. Circuitry means are operatively connected to the detectors for measuring the number of gamma rays detected thereby, the circuitry means typically including a photo multiplier tube and preamplifier operatively connected to each detector, and circuitry means for correcting for random gamma rays detected by the detectors.
According to one aspect of the invention, there is provided a method of optimizing the effect on a living patient of drugs and substances that affect brain chemistry, comprising the steps of: (a) Administering to the patient a tracer substance comprising or consisting of a ligand that binds to presynaptic or postsynaptic neuroreceptors. (b) Waiting a period of time sufficient for the ligand to bind to the neuroreceptors. (c) Measuring emissions from the tracer substance which are indicative of the number of the patient's neuroreceptors and the degree of occupancy or blocking of the patient's neuroreceptors. (d) Calculating the number of neuroreceptors and the degree of occupancy or blocking of the neuroreceptors utilizing a mathematical model computation. (e) Comparing the calculations obtained in step (d) with an intra-person control, if one is available for the patient, or if an intra-person control for the patient is not available, comparing the calculations with an inter-person control, to determine the degree of drug response. And, (f) gauging further treatment of the patient with drugs or substances that affect brain chemistry based upon the comparison made in step (e). The method is applicable to the treatment of schizophrenia, Parkinson's disease, focal epilepsy, tardive dyskinesia, Huntington's disease, and other nervous and mental disorders, and also can be applied to the treatment of drug addictions, as by determining the optimum dosage of methadone to prevent withdrawal, and in the administration of drugs for blocking opiate neuroreceptors (such as Naltrexone).
According to another, specific, aspect of the invention there is provided a method of monitoring the effectiveness of dopamine neuroreceptor blockage of a living schizophrenic patient, comprising the steps of: (a) Administering to the patient a radioactive dopamine receptor blocking drug. (b) Measuring radioactive emissions from the radioactive drug from the time of injection until some predetermined time thereafter, the pre-determined time being related to the half life of the radioactive element in the drug administered. (c) After the radioactive tracer drug has substantially disappeared by radioactive decay, administering to the patient a predetermined dose of dopamine neuroreceptor blocking drug in non-radioactive form. (d) Repeating step (a). (e) Repeating step (b). And, (f) determining the degree of blockade of the dopamine neuroreceptors utilizing the predetermined dose administered in step (c), by comparing the measurements obtained in steps (b) and (e).
According to still another specific aspect of the present invention, there is provided a method of monitoring the effectiveness of the treatment of drug addiction of a patient comprising the steps of: (a) Administering to the patient a radioactive opiate receptor blocking drug. (b) Measuring radioactive emissions from the radioactive drug from the time of injection until some predetermined time thereafter, the pre-determined time being related to the half life of the radioactive element in the drug administered. (c) After the radioactive tracer drug has substantially disappeared by radioactive decay, administering to the patient a predetermined dose of opiate neuroreceptor blocking drug in non-radioactive form. (d) Repeating step (a). (e) Repeating step (b). And, (f) determining the degree of blockade of the opiate neuroreceptors utilizing the predetermined dose administered in step (c), by comparing the measurements obtained in steps (b) and (e).
It is the primary object of the present invention to provide for the effective monitoring of the effect of drugs and substances on brain chemistry. This and other objects of invention will become clear from an inspection of the detailed description of the invention, and from the appended claims.